This project represents a continuing effort toward clarifying possible temporal and pathogenetic relationships of diabetes mellitus to changes in plasma glycoproteins and to renal glomerular microangiopathy. Using the experimental modal of streptozotocin induced diabetes mellitus in the rat, we have, by two dimensional isoelectric focussing gradient polyacrylamide gel electrophoresis, obtained evidence of abnormal high molecular weight protein components in the blood plasma of chronically diabetic rats untreated with insulin. To be defined are (a) the nature and tissue of origin of these proteins; (b) the qualitative and quantitative relation of these proteins to the onset and duration of the diabetes; (c) the effects of treatment with insulin; (d) the relation, if any, to the abnormal protein deposits of renal microangiopathy. The possible relationship of the abnormal proteins to normal constituents of rat plasma will be tested serologically with specific antisera to known rat plasma proteins such as IgG, IgM, fibrinogen, # 1-macroglobulin, # 1-acid glycoprotein (Darcy), # 2 macroglobulin, and C3 component of complement.